Departments of aGenetics and Genomics bPsychiatry, IIS - Fundacion Jimenez Diaz University Hospital cCIBERER ISCIII dDepartment of Biology, Autonomous University of Madrid, CBMSO, CSIC eDepartment of Clinical Pharmacology, La Princesa University Hospital, IIS Princesa fCIBEREHD ISCIII gDepartment of Preventive Medicine, Public Health and Medical Immunology and Microbiology, School of Health Sciences, Rey Juan Carlos University hCIBERSAM ISCIII, Madrid iCICAB, Clinical Research Centre, Extremadura University Hospital and Medical School, Badajoz, Spain jDepartment of Psychiatry, Columbia University, New York, New York, USA.
Pharmacogenet Genomics. 2013 Nov;23(11):627-30. doi: 10.1097/FPC.0b013e3283659a94.
The variability in the antipsychotic response is, to some extent, genetically determined. Several studies have attempted to establish a role for genetic variation in genes coding pharmacokinetic and pharmacodynamic targets, but to date, no definite genetic predictive marker has been identified. We aimed to explore the putative role of 19 genetic variants and risperidone clinical improvement in 76 White schizophrenic inpatients, measured as change in Positive and Negative Syndrome Scale (PANSS). CYP2D6 poor metabolism was significantly associated with greater clinical improvement in total PANSS and a trend was also found for MDR1 3435C>T to higher total PANSS scores in 3435T carriers. This study suggests the importance that genetic variability on pharmacokinetic factors may have in risperidone response and gives evidence for the need for further investigation in order to establish the actual predictive value and clinical utility that CYP2D6 genotyping might have in risperidone therapy management.
抗精神病药反应的变异性在一定程度上是由遗传决定的。有几项研究试图确定编码药代动力学和药效学靶点的基因中的遗传变异的作用,但迄今为止,尚未确定明确的遗传预测标志物。我们旨在探讨 19 种遗传变异和利培酮在 76 名白人精神分裂症住院患者中的临床改善作用,以阳性和阴性综合征量表 (PANSS) 的变化来衡量。CYP2D6 代谢不良与总 PANSS 的更大临床改善显著相关,MDR1 3435C>T 也显示出 3435T 携带者的总 PANSS 评分更高的趋势。这项研究表明,药物代谢动力学因素的遗传变异性可能对抗精神病药的反应具有重要意义,并证明需要进一步研究,以确定 CYP2D6 基因分型在利培酮治疗管理中的实际预测价值和临床应用。